Search Results (581)

Objectives: Inflammatory bowel disease (IBD) is associated with extraintestinal comorbidities, and lung diseases are widespread manifestations. Respiratory bacterial insult is a common illness that results in acute lung injury (ALI) in critical patients. IBD concurrence with respiratory infection may further exacerbate lung injury. Tryptophan (Try), an essential amino acid, is processed by gut microbiota and produces aryl hydrocarbon receptor (AhR) ligands. These ligands can activate the AhR pathway that exerts anti-inflammatory properties and provides protection against mucosal barrier injury. This study investigated the effects of dietary Try on lipopolysaccharide (LPS)-stimulated ALI in mice with colitis induced by dextran sodium sulfate (DSS). Methods: Mice with colitis were allocated to four groups: (1) ND-Sal: normal diet + DSS + intratracheal saline injection; (2) ND-LPS: normal diet + DSS + intratracheal LPS injection; (3) TD-Sal: Try diet + DSS + intratracheal saline injection; (4) TD-LPS: Try diet + DSS + intratracheal LPS injection. Mice were sacrificed 24 h after the intratracheal injection. Results: Results showed that colitis resulted in a high disease activity index. Following induction of ALI in colitis mice, neutrophil populations and inflammatory cytokine levels in bronchoalveolar lavage fluid increased. Gene expression levels associated with toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling were upregulated, and tight junction proteins decreased in the lungs. Dietary Try supplementation decreased circulating LPS levels, suppressed pulmonary TLR4/NF-κB signaling, upregulated AhR/interleukin-22 expression, attenuated oxidative stress and improved the capillary–epithelial barrier integrity in DSS-treated mice. Conclusions: These findings imply that Try may have potential therapeutic significance in bacterial-induced ALI in a colitis condition. Full article

Background: The metastatic dissemination of melanoma involves adhesion of circulating tumor cells within organ-specific vascular beds; however, the relative contribution of the endothelial environment versus that of the melanoma-intrinsic molecular state remains unclear. Materials and Methods: We quantified the in vitro adhesion of primary (n = 5) and metastatic (n = 3) melanoma cell lines to human hepatic, brain, and pulmonary endothelial cells under co-culture conditions, and we profiled the expression of 86 adhesion- and extracellular-matrix-related genes in melanoma and endothelial cells. Results: Adhesion was highest for the hepatic endothelium, intermediate for the pulmonary endothelium, and lowest for the brain endothelium. This endothelial preference was conserved in both primary and metastatic melanoma cells, though metastatic cells exhibited higher absolute adhesion. The linear mixed-effect models revealed that the effects of adhesion state on melanoma gene expression were modest and varied by endothelial type, whereas melanoma origin had more widespread and larger effects (mean absolute standardized coefficients of 0.32–0.47 versus 0.60–0.87, respectively). The expression of three genes (SPP1, ITGA11, and MMP2) was associated with melanoma origin in all endothelial types. Spearman’s co-expression analysis revealed endothelial-type-specific gene networks, and within-sample permutation confirmed the non-random coordination in all three endothelial types. Conclusions: Our findings support a model in which endothelial organ specificity contributes to melanoma cell adhesion behavior and associated transcriptional patterns, highlighting the importance of the vascular interface as a biologically active mediator of early metastatic cell–endothelium interactions. Full article

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly with exceptional survival into adulthood. We present a 66-year-old woman with chest and back pain in whom ALCAPA was diagnosed using coronary computed tomography angiography (CCTA) with curved planar reformation and cinematic volume rendering technique (cVRT). Photorealistic three-dimensional reconstruction provided complementary three-dimensional visualization that may facilitate anatomic understanding and communication of the anomalous origin. Conservative management was adopted given the patient’s age and well-developed collateral circulation. This case underscores the value of advanced CCTA visualization in diagnosing rare coronary anomalies in elderly patients. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based staging and prognostication, tissue and liquid biopsy-based tumor characterization, treatment planning, surgical and intraoperative guidance, and drug discovery. In imaging, deep learning models have demonstrated high performance in pulmonary nodule detection, risk stratification, and prediction of molecular alterations, while also showing promise in improving screening efficiency and reducing interpretive variability. In pathology and liquid biopsy domains, AI enables prediction of driver mutations, immunotherapy response, and survival outcomes directly from histopathology slides, circulating tumor DNA, and other blood-based biomarkers, facilitating minimally invasive precision oncology approaches. In treatment planning and delivery, AI systems are being developed to support clinical decision-making, surgical planning (through advanced image segmentation and delineation of operative anatomy), and intraoperative navigation through robotic and computer vision-enabled platforms. Despite these advances, significant barriers remain, including limited real-world validation, algorithmic biases, workflow integration issues, and unresolved ethical and legal concerns. Future progress will depend on the development of transparent, clinically validated, and generalizable AI systems that augment rather than replace the expertise of clinical providers and healthcare teams. Active engagement from pulmonologists, oncologists, radiologists, and thoracic surgeons will be essential in guiding safe implementation and ensuring that AI-driven innovations translate into meaningful improvements in patient outcomes. Full article

Preterm infants, especially extremely preterm infants under 28 weeks of gestation, face high mortality rates due to respiratory distress resulting from pulmonary immaturity. Conventional mechanical ventilation and extracorporeal membrane oxygenation (ECMO) therapy inevitably cause irreversible lung injury or severe complications, respectively. Here, we developed a microfluidic oxygenator (MO) mimicking the human alveolar-capillary barrier to provide respiratory support for preterm infants. These structures promoted uniform flow distribution, reduced high-shear stress and flow stagnation, and improved gas exchange efficiency. In vitro experiments demonstrated that a single-layer MO raised blood oxygen saturation from 64.7% to 96.5% at 8 mL/min, with a corrected vol% oxygen transfer of 5.24% (52.4 mL O₂/L blood). Hemolysis and coagulation measurements after a 6 h circulation confirmed good hemocompatibility, with most blood damage attributable to the pump. An eight-layer stacked MO was configured with a total priming volume of approximately 5.6 mL and a pressure drop of 25–35 mmHg at 24–40 mL/min, indicating its potential in pumpless extracorporeal circulation for preterm neonates. This MO holds promise for providing minimally invasive and customizable respiratory support in an artificial uterus system. Full article

Iron is essential for life, but its safe use by the body depends on it being kept within tightly controlled compartments. When this compartmentalisation is disrupted—through haemolysis, saturation of scavenger proteins, or dysregulation of the hepcidin–ferroportin axis—damaging iron species accumulate in the circulation and within vascular cells, with potentially serious consequences for endothelial function. This review explores the mechanisms by which iron dysregulation compromises vascular endothelial cell biology across a range of disease states, including haemolytic anaemias, atherosclerosis, cerebrovascular disease, extracorporeal circulatory support, and iatrogenic iron loading. Common pathological themes emerge: depletion of nitric oxide bioavailability, oxidative stress, endothelial activation, and in chronic settings, vascular remodelling. The review subsequently focuses in depth on the pulmonary vasculature, where dysregulated iron compartmentalisation has emerged as a key contributor to the pathogenesis of pulmonary hypertension. Here, iron-driven mitochondrial dysfunction, smooth muscle cell proliferation, and iron-dependent lipid peroxidation via ferroptosis are discussed as mechanistic drivers of pulmonary vascular remodelling. The therapeutic implications of targeting iron handling in pulmonary hypertension are considered, including modulation of the hepcidin–ferroportin axis. Together, the evidence presented highlights disordered iron compartmentalisation as a unifying pathological thread across vascular disease and a compelling target for intervention. Full article

The treatment of intracellular bacterial infections such as Chlamydia remains a significant clinical challenge due to rising antibiotic resistance and persistent, immunopathology-driven tissue damage. Macrophages are essential for host defense; they can originate from both tissue-resident precursors and circulating monocytes. During infection, macrophages at infected sites are largely derived from monocytes that migrate and differentiate there, where they phagocytose pathogens and orchestrate immune responses. The chemokine receptor CCR2 is a key regulator of this process, yet its role beyond monocyte trafficking is not fully understood. Previous studies have shown that CCR2 deficiency impairs monocyte mobilization and exacerbates disease during Chlamydia infection, shifting immune responses away from protective Th1 immunity toward pathological Th2 and Th17 polarization. Here, we investigate how CCR2 regulates macrophage function to balance protective Th1 versus pathological Th2/Th17 immunity during Chlamydia respiratory infection. Our results show that CCR2 deficiency reduces pulmonary infiltration of Ly6C^hi and Ly6C^low monocytes and shifts macrophage differentiation away from an M1-like toward an M2-like phenotype. Mechanistically, CCR2 deficiency compromises macrophage endocytosis and survival, elevates ROS production, and activates the NLRP3 inflammasome, leading to Caspase-3/GSDME-mediated pyroptosis with increased IL-1β and IL-18, while suppressing the Caspase-1/GSDMD pathway. These findings were recapitulated in vitro using C. muridarum-stimulated Ccr2-deficient bone marrow-derived macrophages (BMDMs), which also showed impaired migration, reduced M1-like polarization, diminished endocytosis, and enhanced ROS/NLRP3/pyroptosis. Furthermore, co-culture of these BMDMs with CD4⁺ T cells revealed that Th1 differentiation was inhibited, whereas Th2 and Th17 responses were promoted. Collectively, CCR2 orchestrates monocyte–macrophage function by driving M1-like polarization and inhibiting NLRP3/Caspase-3/GSDME pyroptosis to rebalance Th1/Th2/Th17 immunity, thereby enhancing bacterial clearance while mitigating immunopathological tissue damage during Chlamydia infection. Full article

Tuberculosis (TB) remains a major global public health burden. This study aimed to identify differentially expressed messenger RNAs (mRNAs) and circulating microRNAs (miRNAs) associated with TB and to validate their potential roles in the disease. We performed RNA sequencing (RNA-Seq) on peripheral blood samples from 10 patients with active pulmonary TB and 10 healthy controls, using peripheral blood mononuclear cells (PBMCs) for mRNA sequencing and plasma for miRNA sequencing. Given the exploratory nature of the plasma miRNA data and the limitations of the U6 normalization method, the results for circulating miRNAs will need to be validated using alternative methods in subsequent experiments. A total of 1323 differentially expressed mRNAs and 49 differentially expressed miRNAs were identified. Functional annotation of differentially expressed genes was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, which revealed two TB-associated pathways: “MicroRNAs in cancer” and “Small cell lung cancer.” Two key mRNAs—tumor protein p53 (TP53) and forkhead box protein P1 (FOXP1)—and one key miRNA (hsa-miR-29b-3p) were identified as potential core regulatory factors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation confirmed that the expression patterns of these candidate molecules were consistent with the RNA-Seq results. Three potential candidate molecules associated with TB were ultimately identified, although their disease specificity remains to be determined. Full article

Infants and children suffering from a variety of heart, lung, and blood disorders are known to be at risk of developing systemic or pulmonary vascular disease. Despite progress made in clinical care, these patients continue to experience high morbidity and mortality. There is evidence that an impairment in the L-arginine-NO signaling pathway is involved in the pathogenesis of many of the vascular disorders afflicting children. By boosting NO production, L-citrulline, the amino acid precursor of the NO substrate L-arginine, has the potential to ameliorate vascular diseases in both the systemic and pulmonary circulations. This review will discuss the current status of the use of L-citrulline as a treatment to improve outcomes in pediatric patients suffering from disorders that place them at risk of developing systemic or pulmonary vascular disease. Future directions and the potential therapeutic use of L-citrulline in vascular diseases not yet under clinical investigation will also be discussed. Full article

Background: Hemodynamic failure remains a major determinant of mortality in critical illness, yet its detection is often delayed because conventional monitoring relies predominantly on Eulerian measurements that quantify pressure and flow magnitude without resolving the spatial and temporal organization of circulation. Consequently, clinically significant states of dysfunction may persist despite apparently stable hemodynamic indices. The Geometry of Shock is a conceptual and hypothesis-generating multi-scale framework intended to integrate established cardiovascular physiology with emerging computational approaches for the analysis of circulatory dysfunction. Framework: The proposed framework combines Guytonian venous return physiology and cardiopulmonary interactions with Lagrangian flow topology, geometric representations of circulatory equilibrium, topological data analysis, and physics-constrained inverse modeling. Rather than focusing exclusively on static thresholds of pressure and flow, the framework proposes a structural interpretation of circulation centered on the dynamic organization and coherence of blood transport across cardiovascular domains. Within this paradigm, under-recognized hemodynamic phenotypes—including stressed volume failure, oscillatory shock during spontaneous breathing, macro–microcirculatory decoupling, and pulmonary vascular pressure–flow dissociation—may emerge from disrupted coupling between vascular, cardiac, pulmonary, and microcirculatory systems. These states may represent reversible structural transitions in venous return geometry and cardiopulmonary interaction preceding overt circulatory collapse. Conclusions: By reframing shock as a disorder of circulatory structure and coherence rather than solely a deficit in flow, this framework proposes a mechanistic foundation that may support future approaches aimed at earlier recognition of instability, improved physiological characterization of hemodynamic phenotypes, and future development and prospective validation of physiology-informed computational decision-support strategies in critical care. These concepts remain exploratory and hypothesis-generating rather than clinically validated. Full article

The right ventricle (RV) is a primary determinant of outcomes in cardiac critical care. RV dysfunction independently predicts morbidity and mortality in conditions such as acute coronary syndromes, pulmonary embolism, and cardiogenic shock. This review synthesizes RV evaluation and management by integrating physiologic principles with bedside diagnostic and therapeutic strategies. The RV is exceptionally sensitive to acute afterload increases due to its adaptation to low-pressure pulmonary circulation. Evaluation utilizes a multimodal approach combining echocardiography, invasive hemodynamics, and specifically the pulmonary artery pulsatility index and central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio and biomarkers. Management focuses on three pillars: individualized preload optimization, afterload reduction via selective pulmonary vasodilators, and contractility augmentation with inotropes. For refractory cases, mechanical circulatory support options like Impella RP, ProtekDuo, and VA-ECMO provide critical bridges to recovery or transplantation. Full article

Coronary–bronchial artery fistulas (CBAFs) represent a rare subset of coronary artery fistulas characterised by an abnormal communication between an epicardial coronary artery and the bronchial arterial circulation. Although historically considered incidental findings, the widespread use of multimodality cardiovascular imaging—particularly coronary computed tomography angiography—has led to increasing recognition of these anomalies in contemporary clinical practice. The clinical significance of CBAFs varies widely and depends primarily on fistula size, shunt magnitude, and associated cardiopulmonary conditions. While many small fistulas remain asymptomatic, larger or haemodynamically significant lesions may result in myocardial ischaemia due to coronary steal, ventricular remodelling, pulmonary manifestations such as haemoptysis, and aneurysmal degeneration of the fistulous tract. A comprehensive evaluation typically requires an integrated multimodality approach combining anatomical imaging, functional ischaemia testing, and, in selected cases, invasive haemodynamic assessment. Management strategies range from conservative surveillance in small asymptomatic fistulas to percutaneous or surgical closure in symptomatic or haemodynamically significant lesions. This review provides an updated overview of the epidemiology, pathophysiology, diagnostic evaluation, and management of CBAFs. Particular emphasis is placed on size-based clinical stratification, multimodality imaging strategies, and contemporary therapeutic approaches, with the aim of offering a practical framework for the diagnosis and longitudinal management of patients with this uncommon but clinically relevant coronary anomaly. Full article

Background/Objectives: Early thrombosis of systemic-to-pulmonary artery shunts (SPS) remains a major cause of morbidity and mortality in neonates with duct-dependent pulmonary circulation. Despite advances in surgical technique, no universally accepted perioperative thrombosis-prevention protocol exists. We evaluated the early outcomes of a standardized perioperative thrombosis-prevention protocol applied in neonates undergoing SPS placement. Methods: This single-center case series included nine consecutive neonates undergoing primary modified Blalock–Taussig shunt placement between January 2024 and July 2025. A predefined and standardized perioperative thrombosis-prevention protocol was uniformly applied, incorporating preoperative aspirin when feasible, intraoperative systemic heparinization targeting activated clotting time (ACT) > 300 s, meticulous shunt flushing and de-airing, preferential distal anastomosis to the main pulmonary artery when anatomically suitable, and early postoperative continuous heparin infusion followed by enteral aspirin. The primary endpoint was early shunt thrombosis within 30 days. Results: Median age at surgery was 28 days (range 14–35), and median operative weight was 3.2 kg (range 2.8–3.6). Cardiopulmonary bypass was required in 33.3% of patients. Delayed sternal closure was performed in 22.2%. Despite recognized prothrombotic risk factors—including complex anatomy, hypoplastic pulmonary arteries, and low cardiac output syndrome (33.3%)—no early shunt thrombosis occurred (0/9). There were no reinterventions, no early mortality, and no major bleeding or intracranial hemorrhage. Conclusions: In this single-center neonatal series, implementation of a standardized perioperative thrombosis-prevention protocol was associated with preserved early shunt patency without increased bleeding risk. Although limited by a small sample size, these findings support the feasibility and short-term safety of a standardized perioperative management strategy in neonatal systemic-to-pulmonary shunt surgery. These findings should be considered hypothesis-generating and not evidence of definitive effectiveness. Full article

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20–30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional “second hits”, including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53–86% of heritable PAH and 14–35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH. Full article

Background: The fetal circulatory system is characterized by the presence of physiological vascular shunts—the ductus venosus, foramen ovale, and ductus arteriosus—which enable a significant portion of blood to bypass the pulmonary circulation and partially the hepatic portal system. This mechanism ensures preferential delivery of oxygenated blood to the brain, heart, and upper body. Agenesis of the ductus venosus (ADV) is a rare vascular anomaly associated with diverse anatomical variations and clinical outcomes. Objectives: This systematic review aimed to determine the prevalence of ADV and to assess the frequency of intrahepatic and extrahepatic types. Additional objectives were to identify the most common drainage sites of the umbilical vein (UV) in extrahepatic ADV, evaluate the genetic abnormalities, congenital heart defects, and extracardiac anomalies most frequently associated with ADV, and establish the prognosis of affected fetuses. Methods: A comprehensive literature search was conducted in the PubMed, Embase, and Web of Science databases using predefined and precise inclusion criteria. Results: The overall prevalence of ADV in the general population was 0.05%. The intrahepatic and extrahepatic types occurred with comparable frequencies, accounting for 51.2% and 48.8% of cases, respectively. In extrahepatic ADV, the most common drainage site of the UV was the right atrium (48%). The most frequent genetic abnormalities were trisomy 21 (12%) and Turner syndrome (6%). Among congenital heart defects, ventricular septal defect (22.7%) and atrioventricular septal defect (8.8%) were most prevalent. Functional consequences were observed in 37.4% of fetuses with isolated ADV, most commonly cardiomegaly. Conclusions: ADV is a rare fetal vascular anomaly. With the increasing availability and utilization of prenatal diagnostic techniques, expanding knowledge of this condition and its clinical implications is essential for accurate diagnosis, management, and prognostic assessment. Full article